A fundamental problem in the diagnosis and management of inflammatory bowel disease (IBD) is the real-time identification of lesions that can occur over large areas of the gastrointestinal (GI) tract. The standard of care presently consists of visual examination through a color videoscope, with tissue appearance and color guiding biopsy and clinical decision making. Given that IBD has a prevalence of over 1.4 million patients in the US alone, and intervention early in the disease course prevents morbidity, new tools to improve diagnostic accuracy, quantify disease burden, and monitor treatment efficacy are desperately needed. The hypothesis guiding this study is that near-infrared (NIR) light, which penetrates several millimeters into the intestinal mucosa, combined with recent advances in structured illumination, will permit real-time quantification of tissue optical properties, inclding perfusion, hydration, and metabolism during colonoscopy, thus improving IBD detection. Although other optical techniques such as optical coherence tomography (OCT), scattering spectroscopy, and absorption spectroscopy have already been applied to the identification of IBD, none provide quantification of optical properties in a wide field (tens of cm2) and non-contact configuration. Recent developments in the mentor's and co-mentor's laboratories provide ultra-fast, non-contact imaging of tissue optical properties during open surgery. Using multispectral spatial frequency domain imaging (SFDI), quantification of reduced scattering and absorption parameters, as well as the chromophores oxyhemoglobin, deoxyhemoglobin, water, and lipid, is now possible. Application of SFDI to minimally invasive techniques, such as colonoscopy and laparoscopy, however, has not yet been attempted because of formidable technical challenges in the correction of tissue curvature and in the production of fiberscope- compatible structured illumination having the proper spatial frequency content. The Specific Aims of this K01 application focus on: 1) developing the optical theory necessary for extracting chromophore concentration from simplified patterns of light, 2) designing a colonoscope projection and acquisition system optimized for simultaneous color video imaging (i.e., the standard of care) and SFDI, and 3) developing an optical metric comprised of various tissue optical properties that is predictive of IBD in a mouse model of the disease. Candidate / Mentors / Environment: The candidate's long-term career goal is to develop novel biomedical technologies and devices that are used in the clinic to improve patient management. The academic environment available at the BIDMC under Dr. Frangioni's guidance, and at the Beckman Laser Institute under Dr. Tromberg's guidance, are ideal for reaching this goal. In order to better respond to needs of clinicians, the candidate needs to learn more about the clinical work environment, and in order to expand his expertise, needs advanced training in biomedical optics theory. The K01 project aims at solving a longstanding problem in IBD diagnosis while training the candidate to become an independent investigator. To achieve this challenging goal, a strong and dedicated mentoring team has been assembled as follows: Name role Summary of the contributions to the project John V. Frangioni, M.D., Ph.D. Mentor Prof. Frangioni will provide specific teaching in clinical translation & biomedical engineering. He will also provide teaching in laboratory management and career development. Bruce J. Tromberg, Ph.D. Co-Mentor Prof. Tromberg will provide specific teaching in biomedical optics theory with a particular focus on advanced techniques such as structured illumination and spectroscopy. Ram Chuttani, M.D. Clinical Consultant Dr. Chuttani will provide specific teaching in gastroenterology clinical workflow, current standard of care in IBD screening and videoendoscopy/fiberoscopy. Robert D. Odze, M.D. Clinical Consultant Prof. Odze will provide specific teaching in IBD histopathology and disease development. He will also help in correlating the optical results with histological findings. Long Ngo, Ph.D. Consultant Dr. Ngo will provide specific teaching in biostatistics and study design. In particular, he will help with the dta analysis for creating and validating the proposed optical IBD index. In summary, this K01 application describes a training vehicle for an applicant with a strong background in intraoperative imaging but with relatively little experience in endogenous diffuse optics, animal studies, and clinical fiberoscopy. The mentor's laboratory has a proven track record in clinical translation of optical technology. The co-mentor's laboratory has expertise in biomedical optics theory. Within this academic environment, the K01 application describes a career development plan and institutional commitment that will permit the transition of the candidate to independence over a period of five years, while he simultaneously contributes to an area of investigation with profound clinical significance. PUBLIC HEALTH RELEVANCE: Inflammatory bowel disease, comprised of Crohn's disease and ulcerative colitis, affects over 1.4 million patients in the United States. It is characterizedby waxing and waning inflammation of the intestinal mucosa that leads to significant pain and suffering. Identification of inflammatory disease in the early stages of a disease flare provides the gastroenterologist with the chance to intervene with medical treatment, thus minimizing morbidity and often avoiding surgery. Unfortunately, only a small fraction of inflammatory bowel lesions can be identified using conventional colonoscopy. This K01 application focuses on the application of a new type of optical imaging, called spatial frequency domain imaging, to colonoscopy for the sensitive and accurate identification of inflammatory bowel disease. This application also serves as a training vehicle for a promising young scientist whose long-term career goal is independent investigation.